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Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma Xin Yuan Shu-Wen Chen Xin-Rui Yi Xin-Yu Li Yi Wang Yun-Shu Tang Min xue mei-Zi Zhu Jin Peng xue-Jin lu Jian-Zhen Huang Zi-Chen Song Chong Wu Ke-Zhong Zheng Qing-Qing Dai Fan Huang Hao-Shu Fang Department of Pathophysiology Anhui Medical UniversityHefeiAnhui 230032China Laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China College of Animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain ***,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP ***,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory *** total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD *** on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating *** study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

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Peroxisome proliferator-activated receptor gamma coactivator-1(PGC-1)family in physiological and pathophysiological process and diseases

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1249-1292页

作者： lu Qian Yanli Zhu Chao Deng Zhenxing Liang Junmin Chen Ying Chen xue Wang Yanqing Liu Ye Tian Yang Yang Xi'an Key Laboratory of Cardiovascular and Cerebrovascular Diseases Xi'an No.3 HospitalThe Affiliated Hospital of Northwest UniversityNorthwest UniversityXi'an 710021China Xi'an Key Laboratory of Innovative Drug Research for Heart Failure Faculty of Life Sciences and MedicineNorthwest University229 Taibai North RoadXi'an 710069China Department of Cardiovascular Surgery The First Affiliated Hospital of Xi'an Jiaotong University277 Yanta West RoadXi'an 710061China Department of Cardiothoracic Surgery The First Affiliated Hospital of Zhengzhou University1 Jianshe EastZhengzhou 450052China Department of Hematology The First Affiliated Hospital of Xi'an JiaotongUniversity277 Yanta West RoadXi'an 710061China

Peroxisome proliferator-activated receptor gamma coactivator-1(PGC-1)family(PGC-1s),consisting of three members encompassing PGC-1a,PGC-1β,and PGC-1-related coactivator(PRC),was discovered more than a quarter-century ***-1s are essential coordinators of many vital cellular events,including mitochondrial functions,oxidative stress,endoplasmic reticulum homeostasis,and *** evidence has shown that PGC-1s are implicated in many diseases,such as cancers,cardiac diseases and cardiovascular diseases,neurological disorders,kidney diseases,motor system diseases,and metabolic *** the upstream modulators and co-activated partners of PGC-1s and identifying critical biological events modulated by downstream effectors of PGC-1s contribute to the presentation of the elaborate network of ***,discussing the correlation between PGC-1s and diseases as well as summarizing the therapy targeting PGC-1s helps make individualized and precise intervention *** this review,we summarize basic knowledge regarding the PGC-1s family as well as the molecular regulatory network,discuss the physio-pathological roles of PGc-1s in human diseases,review the application of PGC-1s,including the diagnostic and prognostic value of PGC-1s and several therapies in pre-clinical studies,and suggest several directions for future *** review presents the immense potential of targeting PGC-1s in the treatment of diseases and hopefully facilitates the promotion of PGC-1s as new therapeutic targets.

关键词： diseases life precise

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Integrating machine learning and CALPHAD method for exploring low-modulus near-β-Ti alloys

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Rare Metals 2024年第1期43卷 309-323页

作者： Hao Zou Yue-Yan Tian Li-Gang Zhang Ren-Hao xue Zi-Xuan Deng Ming-Ming lu Jian-Xin Wang Li-Bin Liu School of Computer Science and Engineering Central South UniversityChangsha 410083China School of Materials Science and Engineering Central South UniversityChangsha 410083China State Key Laboratory of Powder Metallurgy Central South UniversityChangsha 410083China

Traditional theoretical and empirical calculation methods can guide the design of β-and metastable β-alloys for bio-titanium. However, it is still difficult to obtain novel near-β-Ti alloys with low modulus. This study developed a method that combines machine learning with calculation of phase diagrams(CALPHAD) to facilitate the design of near-β-Ti alloys. An elastic modulus database of Ti–Nb–Zr–Mo–Ta–Sn system was constructed first, and then three features(the electron to atom ratio, mean absolute deviation of atom mass, and mean electronegativity) were selected as the key factors of modulus by performing a three-step feature selection. With these features, a highly accurate model was built for predicting the modulus of near-β-Ti alloys. To further ensure the accuracy of modulus prediction, machine learning with the elastic constants calculated was leveraged by CALPHAD database. The root mean square error of the well-trained model can be as low as 6.75 GPa. Guided by the prediction of machine learning and CALPHAD, three novel near-β-Ti alloys with elastic modulus below 50 GPa were successfully designed in this study. The best candidate alloy(Ti–26Nb–4Zr–4Sn–1Mo–Ta) exhibits an ultra-low modulus(36.6 GPa) after cold rolling with a thickness reduction of 20%. Our method can greatly save time and resources in the development of novel Ti alloys, and experimental verifications have demonstrated the reliability of this method.

关键词： Near-β-Ti alloy Machine learning Calculation of phase diagram Low-modulus alloy Feature selection

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Advanced Materials for NH_(3)Capture:Interaction Sites and Transport Pathways

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Nano-Micro Letters 2024年第11期16卷 119-155页

作者： Hai‑Yan Jiang Zao‑Ming Wang xue‑Qi Sun Shao‑Juan Zeng Yang‑Yang Guo lu Bai Ming‑Shui Yao Xiang‑Ping Zhang Key Laboratory of Green Process and Engineering State Key Laboratory of Mesoscience and EngineeringBeijing Key Laboratory of Ionic Liquids Clean ProcessInstitute of Process EngineeringChinese Academy of SciencesBeijing 100190People’s Republic of China School of Future Technology University of Chinese Academy of SciencesBeijing 100049People’s Republic of China China University of Petroleum Beijing 102249People’s Republic of China Institute for Integrated Cell‑Material Sciences(iCeMS) Kyoto UniversitySakyo‑KuYoshidaKyoto 606‑8501Japan

Ammonia(NH3)is a carbon-free,hydrogen-rich chemical related to global food safety,clean energy,and environmental *** an essential technology for meeting the requirements raised by such issues,NH3 capture has been intensively explored by researchers in both fundamental and applied *** four typical methods used are(1)solvent absorption by ionic liquids and their derivatives,(2)adsorption by porous solids,(3)abadsorption by porous liquids,and(4)membrane *** in the development of advanced materials for NH3 capture,we conducted a coherent review of the design of different materials,mainly in the past 5 years,their interactions with NH3 molecules and construction of transport pathways,as well as the structure–property relationship,with specific examples ***,the challenges in current research and future worthwhile directions for NH3 capture materials are proposed.

关键词： Ammonia capture Solvents Porous solids Porous liquids Membranes

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Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 4006-4013页

作者： Zu-Gui Tang Tie-mei Chen Yi lu Zhe Wang Xi-Cheng Wang Yi Kong Department of Oncology The First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhou 510080Guangdong ProvinceChina Faculty of Pharmaceutical Sciences Shenzhen University of Advanced TechnologyShenzhen 518000Guangdong ProvinceChina Guangdong Pharmaceutical University Guangzhou 510006Guangdong ProvinceChina

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective ***(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side *** study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their *** To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in *** Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking ***-GEM through electroporation,sonication,or incubation,and the loading efficiency was *** cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry *** The isolated exosomes had an average size of 76.7 *** encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than *** cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 ***,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell *** Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.

关键词： Mesenchymal stem cells Exosomes Extracellular vesicles Gemcitabine Pancreatic cancer Drug delivery

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Spi1 regulates the microglial/macrophage inflammatory response via the PI3K/AKT/mTOR signaling pathway after intracerebral hemorrhage

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Neural Regeneration Research 2024年第1期19卷 161-170页

作者： Guoqiang Zhang Jianan lu Jingwei Zheng Shuhao mei Huaming Li Xiaotao Zhang An Ping Shiqi Gao Yuanjian Fang Jun Yu Department of Neurosurgery The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang ProvinceChina Department of Neurosurgery Huashan Hospital of Fudan University School of MedicineShanghaiChina Clinical Research Center for Neurological Diseases of Zhejiang Province HangzhouZhejiang ProvinceChina Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases HangzhouZhejiang ProvinceChina

Preclinical and clinical studies have shown that microglia and macrophages participate in a multiphasic brain damage repair process following intracerebral *** E26 transformation-specific sequence-related transcription factor Spi1 regulates microglial/macrophage commitment and ***,the effect of Spi1 on intracerebral hemorrhage remains *** this study,we found that Spi1 may regulate recovery from the neuroinflammation and neurofunctional damage caused by intracerebral hemorrhage by modulating the microglial/macrophage *** showed that high Spi1expression in microglia/macrophages after intracerebral hemorrhage is associated with the activation of many pathways that promote phagocytosis,glycolysis,and autophagy,as well as debris clearance and sustained ***,microglia with higher levels of Soil expression were chara cterized by activation of pathways associated with a variety of hemorrhage-related cellular processes,such as complement activation,angiogenesis,and *** conclusion,our results suggest that Spi1 plays a vital role in the microglial/macrophage inflammatory response following intracerebral *** new insight into the regulation of Spi1 and its target genes may advance our understanding of neuroinflammation in intracerebral hemorrhage and provide therapeutic targets for patients with intracerebral hemorrhage.

关键词： intracerebral hemorrhage macrophage microglia neuroinflammation phagocytosis PI3K/AKT/mTOR signaling pathway Spi1 transcriptomics

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QL1706 (anti-PD-1 IgG4/CTLA-4 antibody) plus chemotherapy with or without bevacizumab in advanced non-small cell lung cancer: a multi-cohort, phase II study

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Signal Transduction and Targeted Therapy 2024年第2期9卷 797-806页

作者： Yan Huang Yunpeng Yang Yuanyuan Zhao Hongyun Zhao Ningning Zhou Yaxiong Zhang Likun Chen Ting Zhou Gang Chen Ting Wu lu lu Shilin xue Xiaoyan Kang Li Zhang Wenfeng Fang Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineNo.651 Dongfeng East RoadGuangzhouGuangdong 510060China Department of Medicine Qilu Pharmaceutical Co.Ltd.JinanChina

First-line chemoimmunotherapy(with or without bevacizumab)has improved outcomes in advanced non-small cell lung cancer(NSCLC).Here,this open-label,multi-cohort phase II study(NCT05329025)was done to investigate the safety and efficacy of QL1706(a single bifunctional MabPair product against PD-1 and CTLA-4)and chemotherapy with or without bevacizumab in this *** were enrolled into five different cohorts based on genotype(cohorts 1-4,epidermal growth factor receptor[EGFR]wild-type;cohort 5,EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors[TKIs]).Between June 11,2021 and December 29,2021,91 patients were *** frequent treatment-related adverse events(TRAEs)included decreased appetite(60[65.9%]),anemia(60[65.9%]),infusion-related reactions(48[52.7%]),and pruritus(44[48.4%]).Grade≥3 TRAEs occurred in 30(33.0%)***-seven(45%)patients with wild-type EGFR achieved partial response(PR)(objective response rate[ORR]=45%)and had a median progression-free survival(mPFS)of 6.8 months(95%CI:5.2-9.7).For 31 patients harboring mutated EGFR,17(54.8%)achieved PR(ORR=54.8%),with an mPFS of 8.5 months(95%CI:5.72-not evaluable).Overall,QL1706 plus chemotherapy,regardless of having bevacizumab,was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line ***,QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy,demonstrating a potential for treating this population.

关键词： bevacizumab chemotherapy phase

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KTP激光泪道术治疗泪道阻塞的临床观察

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国际眼科杂志 2008年第5期8卷 1040-1041页

作者：杨建华卢雪梅鲁文书中国江苏省东台市富东医院眼科 224200

目的：观察KTP激光泪道术治疗泪道阻塞的效果,并探讨治疗失败的原因。方法：分析泪道阻塞196例（201眼）经KTP激光治疗资料。结果：201眼经激光治疗后,随访4～12mo,有效169眼,其中复合性阻塞者有效率较低。结论：KTP激光泪道术操作简便... 详细信息

目的：观察KTP激光泪道术治疗泪道阻塞的效果,并探讨治疗失败的原因。方法：分析泪道阻塞196例（201眼）经KTP激光治疗资料。结果：201眼经激光治疗后,随访4～12mo,有效169眼,其中复合性阻塞者有效率较低。结论：KTP激光泪道术操作简便,组织损伤小,可有效治疗各类泪道阻塞。失败原因主要是复合性阻塞与假道形成等。

关键词： KTP激光泪道术泪道阻塞临床研究治疗方法

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Printability disparities in heterogeneous material combinations via laser directed energy deposition:a comparative study

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International Journal of Extreme Manufacturing 2024年第2期6卷 389-405页

作者： Jinsheng Ning Lida Zhu Shuhao Wang Zhichao Yang Peihua Xu Pengsheng xue Hao lu Miao Yu Yunhang Zhao Jiachen Li Susmita Bose Amit Bandyopadhyay School of Mechanical Engineering and Automation Northeastern UniversityShenyang 110819People’s Republic of China School of Machinery and Automation Wuhan University of Science and TechnologyWuhan 430081People’s Republic of China School of Mechanical Engineering Xi’an University of Science and TechnologyXi’an 710054People’s Republic of China Beijing Institute of Space Launch Technology Beijing 100076People’s Republic of China W.M.Keck Biomedical Materials Research Lab School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America

Additive manufacturing provides achievability for the fabrication of bimetallic and multi-material structures;however,the material compatibility and bondability directly affect the parts’formability and final *** is essential to understand the underlying printability of different material combinations based on an adapted ***,the printability disparities of two common and attractive material combinations(nickel-and iron-based alloys)are evaluated at the macro and micro levels via laser directed energy deposition(DED).The deposition processes were captured using in situ high-speed imaging,and the dissimilarities in melt pool features and track morphology were quantitatively investigated within specific process ***,the microstructure diversity of the tracks and blocks processed with varied material pairs was comparatively elaborated and,complemented with the informative multi-physics modeling,the presented non-uniformity in mechanical properties(microhardness)among the heterogeneous material pairs was *** differences in melt flow induced by the unlike thermophysical properties of the material pairs and the resulting element intermixing and localized re-alloying during solidification dominate the presented dissimilarity in printability among the material *** work provides an in-depth understanding of the phenomenological differences in the deposition of dissimilar materials and aims to guide more reliable DED forming of bimetallic parts.

关键词： directed energy deposition printability microstructure microhardness bimetallic parts

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Spontaneous anchoring Cl intoα-Co(OH)_(2) as efficient and stable oxygen reduction electrocatalysts for seawater battery

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Rare Metals 2024年第7期43卷 3074-3083页

作者： Wang Zheng xue-Rong Zheng Qi lu Yan-Hui Cao Yang Wang Hai-Peng Fu Jin-Feng Zhang Yi-Da Deng Wen-Bin Hu School of Materials Science and Engineering Key Laboratory of Advanced Ceramics and Machining Technology of Ministry of EducationTianjin UniversityTianjin 300072China State Key Laboratory of Marine Resource Utilization in South China Sea School of Materials Science and EngineeringHainan UniversityHaikou 570228China Key Laboratory of Electromagnetic Processing of Materials Ministry of EducationNortheastern UniversityShenyang 110819China

Seawater battery is an advanced energy storage system that enables conversion of chemical energy to electricity by consuming metals,dissolved oxygen and seawater in anode,cathode and electrolyte,***,the oxygen reduction reaction(ORR)activity and stability of electrocatalysts can be easily deactivated due to the severe Cl~-permeation and corrosion in seawater ***,we developed a structural buffer engineering strategy by spontaneously anchoring Cl~-intoα-Co(OH)_(2) as efficient and stable ORR electrocatalysts,in which the ultrathinα-Co(OH)_(2) nanosheets were synthesized using an ultrafast solution high-temperature shock(SHTS)*** large lattice space(~0.8 nm)of layeredα-Co(OH)_(2) ensured the spontaneously penetration of Cl~-into the lattice structure and replaced part of OH~-to formα-Co(OH)_(2-x)Cl_*** continuous leaching and compensating of saturated Cl inα-Co(OH)_(2-x)Cl_x could enhance the Cl~-corrosion resistance and modulate electronic structure of Co metallic sites,thus improving the ORR electrocatalytic activity and stability in seawater ***α-Co(OH)_(2-x)Cl_x seawater batteries display superior onset and half-wave potentials of 0.71 and 0.66 V,respectively,which are much better than the counterparts ofα-Co(OH)_(2) and ofβ-Co(OH)_(2) with no Cl~-penetrating and no buffer ***α-Co(OH)_(2-x)Cl_x-based seawater batteries display stable open-circuit potential of 1.69 V and outstanding specific capacity of 1345 mAh·g^(-1).

关键词： Seawater battery Oxygen reduction electrocatalyst Solution high-temperature shock Structural buffer engineering

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